title: Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors.
abstract: BACKGROUND
  Chemotherapy-associated neutropenia has been reported to be a pharmacodynamic marker of response in some advanced solid tumors. Factors that accelerate drug clearance lead to lower plasma concentrations and toxicity, including neutropenia. Smoking accelerates the metabolism of several drugs, including chemotherapy. We sought to study the effects of smoking on gemcitabine-induced neutropenia in this retrospective study.
  
  
  METHODS
  Smoking status and neutropenia along with other clinical parameters were recorded in 151 patients receiving first-line gemcitabine-based chemotherapy for advanced solid tumors.
  
  
  RESULTS
  Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary (70.9%), or other/unknown primary cancer (15.2%). Logistic regression showed that never smokers had increased neutropenia versus current smokers (odds ratio: 3.5; 95% confidence interval, CI: 1.1-11.4). A 5-unit increase in pack-years reduced the odds of having higher neutropenia toxicity by 6.3% (95% CI 12 to 1%; p = 0.036).
  
  
  CONCLUSIONS
  Smokers had less neutropenia than nonsmokers, a finding that was more pronounced with increasing pack-years. This pharmacodynamic marker of gemcitabine-induced neutropenia may result in less efficacy of gemcitabine. Future prospective trials should correlate smoking, metabolizing phenotype, neutropenia, and response to gemcitabine therapy.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Michigan, Ann Arbor, Mich., USA.
authors.forename: Meaghan
authors.initials: M
authors.lastname: O'Malley
authors.forename: Patrick
authors.initials: P
authors.lastname: Healy
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault
authors.forename: Nithya
authors.initials: N
authors.lastname: Ramnath
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D012907:Smoking / Q000503:physiopathology*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine